Krüppel-like factor 6 rendered rat Schwann cell more sensitive to apoptosis via upregulating FAS expression

PLoS One. 2013 Dec 4;8(12):e82449. doi: 10.1371/journal.pone.0082449. eCollection 2013.

Abstract

Krüppel-like factor 6 (KLF6) is a tumor suppressor gene and play a role in the regulation of cell proliferation and apoptosis. After the peripheral nerve injury (PNI), the microenvironment created by surrounding Schwann cells (SCs) is a critical determinant of its regenerative potential. In this study, we examined the effects of KLF6 on SCs responses during PNI. Both KLF6 mRNA and protein expression levels were upregulated in the injured sciatic nerve, and immunofluorescence results showed that many KLF6-positive cells simultaneously expressed the SC markers S-100 and p75NTR. The apoptosis inducers TNFα and cisplatin upregulated KLF6 expression in primary cultured SCs and the SC line RSC96. Although KLF6 overexpression exacerbated cisplatin- and TNFα-induced apoptosis, expression levels of the apoptosis regulators Bcl2 and Bax were not significantly affected in either KLF6-overexpressing or KLF6-depleted RSC96 cells. Realtime PCR arrays and qRT-PCR demonstrated that KLF6 overexpression upregulated four pro-apoptotic genes, FAS, TNF, TNFSF12, and PYCARD, and inhibited expression of the anti-apoptotic IL10 gene expression. Further analysis revealed that FAS protein expression was positively correlated with KLF6 expression in SCs. These data suggest that KLF6 upregulation may render SCs more vulnerable to apoptosis after injury via upregulating FAS expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Gene Expression Regulation*
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Male
  • Peripheral Nerve Injuries / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Receptors, Death Domain / metabolism
  • Schwann Cells / metabolism*
  • Sciatic Nerve / injuries
  • Sciatic Nerve / metabolism
  • Signal Transduction
  • bcl-2-Associated X Protein / metabolism
  • fas Receptor / genetics*

Substances

  • Klf6 protein, rat
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors
  • Proto-Oncogene Proteins
  • Receptors, Death Domain
  • bcl-2-Associated X Protein
  • fas Receptor

Grant support

This study was supported by the national natural science foundation of china, project number: 81271380; Shanghai Science and technology foundation of China, project number: 1052nm04200; The international cooperation projects of Shanghai science and technology committee, project number: 09410706200. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.